Re: [AMBER] obtain or build parameters for non-natural residues

From: David Cerutti <>
Date: Mon, 23 May 2016 10:12:23 -0400

Hi Aline,

If you want to fight the good fight and make parameters de-novo, I can walk
you through a pipeline for this. It's something I'm (very) actively
developing, but we're just getting ready to submit the manuscript for the
second-generation protein force field. The charges will be relatively
simple to create, and for the cases you've identified I would imagine that
only retyping CB and CG atoms, respectively, would be necessary, which
greatly limits the number of torsion parameters that would need to be
fitted. There are three protein force fields currently distributed with
Amber: ff14SB, ff15ipq, and FB15. The first and third use the Cornell
charges first minted in 1995, which are very much like what you'd get if
you were to use the R.E.D. server that Karl mentioned. The charges on
ff15ipq are of a different breed, using a protocol I developed with some
IBM people in 2010.

Whichever charge set you use, you'll need some new torsions. I would
recommend you inherit backbone torsions from whatever force field you
choose to model your nonstandard amino acids after, and when you do that
it's also a good idea to inherit the charges on backbone atoms. I would
imagine that R.E.D. server lets you peg charges to pre-defined values, but
if not I know exactly how to do this in my AmberTools program.

So, the workflow I'd see here is that you pick one of ff14SB (standard
Amber protein model), ff15ipq (hot off the presses, complete rederivation
of charges and bonded parameters with an updated physics model), or fb15
(ff14SB charges with rederivation of bonded parameters). Then, make your
library files for the amino acids as they will appear in the protein
(main-chain or terminal groups... just need to know about how they connect
to other residues), refit charges appropriate to whichever protein force
field you chose, differentiate the atom types starting at the point along
the side chain that these amino acids become "nonstandard," and finally
make some conformations and do the torsion fitting.


On Mon, May 23, 2016 at 3:31 AM, Karl Kirschner <>

> Hello Aline,
> The model development of nonstandard residues is a difficult thing to do.
> The main issues that one has to consider include a) determining partial
> atomic charges that are balanced with your desired force field, b) are
> there atom types that already exist in desired force field that can be used
> to describe your molecule, or will you need to create new atom types c)
> choosing the Lennard-Jones parameters for new atom types, d) parameterizing
> any missing bond, angle, and torsion parameters using target experimental
> and/or quantum data. Amber's antechamber program is a good place to start,
> which can provide AM1-BCC charges easily and approximate missing
> parameters. However, to truly optimize bonded parameter one needs to use
> target experimental and/or QM data, which can be very time consuming since
> you might need to generate QM potential energy curves of various internal
> coordinates. The R.E.D. server is a good place for determining more robust
> charges that are balanced with a given force field. The other thing to
> consider is if these nonstandard residues will be used as part of the
> primary sequence of a protein, or if they will be used a nonbonded ligands.
> In the former case, one needs to make sure the charges and parameters are
> balanced with the protein force field. In the later case, one has the
> option of using the GAFF force field for modeling the ligand component.
> Bests,
> Karl
> On Fri, May 20, 2016 at 9:45 AM, ALINE THOMAS <
>> wrote:
> > Dear Amber users and developers
> >
> > I am looking for .lib or .frcmod files for amber for two non-natural
> > residues
> > as gamma-carboxylic glutamic acid (GLA) and beta-hydroxy-aspartate
> > residues (BHA),
> > could not find anything on the archive, or from any website (PTM, NCAA,
> > Bryce lab...)
> >
> > would you have any helping advice for obtaining them
> > or for building them de novo ? never done that,
> >
> > Thank you very much for your help
> >
> > Aline
> >
> >
> > --
> > Aline Thomas, PhD
> >
> > Département de Pharmacochimie Moléculaire
> > Université Joseph Fourier BP53
> > 470, rue de la chimie
> > 38041 Grenoble cedex 9
> > Tél : +33 (0)
> > Fax : +33 (0)
> >
> >
> > _______________________________________________
> > AMBER mailing list
> >
> >
> >
> --
> Karl. N. Kirschner, Ph.D.
> Research Associate
> Bonn-Rhein-Sieg University of Applied Sciences
> Grantham-Allee 20, 54757 Sankt Augustin, Germany
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Received on Mon May 23 2016 - 07:30:02 PDT
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